G15

Question 1

what are CDCV

Answer 1

common diseases use to common variants

Question 2

what are common variants

Answer 2

polymorphisms that occur at 1-5% in populations

Question 3

what are the two hypotheses for common variants

Answer 3

1. common diseases are due to common variants, several genes contribute, each polymorphism is of small effect - can be detected via association studies
2. common diseases are due to rare alleles of large effect, - cant be detected via association studies

Question 4

what is the more common correlation between effect size and allele frequency

Answer 4

more likley to get common variants with small effect sizes identified by GWAS
highly penetrant alleles for mendellian disorders are extremely rate with large effect sizes

Question 5

what is the equation for linkage disequilibrium

Answer 5

D= PABPab - PAbPaB

Question 6

How do you calculate the coefficient of disequilibirum

Answer 6

r^2 = D^2/ PAPaPBPb

Question 7

what values can the coefficient of disequilbirum take

Answer 7

range from 0-1
0 = linkage equilibirum
1 = linkage disequilbirum

Question 8

what do hotspots of recombination produce

Answer 8

blocks of LD in the genome - variation in each block is low

Question 9

in theory how many SNPs do you need to analyze to determine if LD is complete

Answer 9

only 1 as if LD then should be same

Question 10

what does local LD result in

Answer 10

SNPs being inherited in haplotype blocks

Question 11

how are control groups selected in population based case/control studies

Answer 11

age matched
sex matched
ethnicity matched
environment matched 
- so differences in marker allele freq in patient population its due to genotypwe

Question 12

how do you calculate reltative risk of disease

Answer 12

P(disease|exposed to allele) / P(disease| no exposed to allele)
can calculate each using a(a/b) and c/(c+d)
a is case exposed
b is control exposed
c = case unexposed
d = control unexposed

Question 13

what does RR of 1-1.5 tell you

Answer 13

small effect

Question 14

what does RR of >2 tell you

Answer 14

large effect

Question 15

what does a manhattan plot show you

Answer 15

human chromosomes shown, with SNPs associated with disease highlighted.

Question 16

what does manhattan plot of T2D and FTO fat mass and obesity associated genes show

Answer 16

clusters of SNPs located within first intron associated.
position 16q12
one FTO SNP has high associated with very low P value
The risk allele frequency was at a higher frequency in the case group.

Question 17

what did FTO studies in transgenic mice show

Answer 17

FTO deletion = lean
FTO dominant missense = lean
FTO over expression = increase fat mass, food intake and body weight
males 10% increase - females more

Question 18

what did risk allele A of an SNP at rsl9939609 show

Answer 18

associated with increased BMI in eypreans homos = 16% pop are at high risk compared to TT homos
AA = eat more, especially fats

Question 19

what are the issues with GWAS?

Answer 19

replication between studies isnt good
questionable clinical utility - hasnt got that dfar
`

Question 20

what did twn studies show about heritability for obestiy adn what did GWAS findings show

Answer 20

40-70%

GWAS found 75 vairants for obesity which explains 2-3% of the phenotypic variation - suggests CDCV doesnt hold.

Question 21

what is an eQTL

Answer 21

genetic loci that affect mRNA expression level of other genes, measured mRNA or protein trait is almost always the product of a single gene with a specific chromosomal location
uses GWAS qtl mappinh approach but maps expression of a particular gene against SNP markers

Question 22

what did eQTL studies for expression of FTO SNPs show

Answer 22

that SNPs associated with BMI are associated with IRX3 expression not FTO in human brain tissue.